ALCO2-FUNC · A Remote-carboxylation Strategy for Alcohols via a Dual-catalytic System

A Remote-carboxylation Strategy for Alcohols via a Dual-catalytic System

The ability to introduce functionality into molecules in a regio- and chemoselective manner is of primary importance in the construction of high value molecular compounds, but still remains a major challenge for synthetic chemists. The utilization of functionalities present in readily available and inexpensive starting materials to direct the introduction of further complexity is an attractive strategy which has become increasingly popular. Despite recent advances, the remote functionalization of aliphatic alcohols still remains largely underdeveloped. Considering their prevalence in natural products, pharmaceuticals and chemical feedstocks, efforts to address this problem were deemed necessary. ALCO2-FUNC aimed to merge (reductive) nickel catalysis with photoredox catalysis to exploit advantages of both disciplines, enabling the development of a divergent strategy by careful control of key catalytic steps (Figure 1). Moreover, carbon dioxide was to be utilized as an abundant and economical C1 synthon to provide a valuable carboxylation strategy. See Figure 1 The development of mild and green synthetic procedures to quickly and selectively produce active pharmaceutical agents is of great importance for global health as it streamlines the discovery and production processes, resulting in less time to market and to benefit those in need. In addition, the application of carbon dioxide is also relevant, as it contributes to the circular economy concept, where waste CO2 streams can be used to produce value-added chemicals. The main objective of ALCO2-FUNC was to develop site-selective, catalytic C–C bond-formation of abundant aliphatic alcohols at distal sp3 C–H sites, thus turning simplicity into complexity for accessing valuable products from simple precursors. The specific objectives were the following: 1. To implement a β-carboxylation of alcohols with CO2 via dual photoredox/ nickel-catalysis. 2. To enable a remote-carboxylation of aliphatic alcohols with CO2 at distal sp3 C–H sites via a chain-walking scenario. 3. To perform electrochemical and mechanistic study on key Ni-alkyl species.

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